The key findings of the present study are that ZNF687 overexpression contributes to CSC-like traits and promotes the tumor formation, invasion, and chemoresistance capabilities of HCC cells, and that ZNF687 can directly upregulate the transcription of the pluripotency-associated factors BMI1, NANOG and OCT4. Importantly, elevated ZNF687 expression in human HCC tissues was closely correlated with poorer overall survival and relapse-free survival, indicating that ZNF687 might represent a valuable prognostic factor and potential target in HCC therapy. Here, ZNF687 is linked to neoplasm.